Cytoreduction Followed by Normothermic Versus Hyperthermic Intraperitoneal Intraoperative Chemoperfusion (HIPEC): a Study in Peritoneal Carcinomatosis

Phase II Study Comparing Normothermic Versus Hyperthermic Intraoperative Chemoperfusion With Oxaliplatin in Patients With Peritoneal Metastases From Appendiceal or Colon Cancer

Peritoneal carcinomatosis from appendix or colon (large bowel) cancer is treated in suitable patients with surgery followed by instillation of heated chemotherapy inside the abdominal cavity. This procedure is termed 'Hyperthermic intraoperative Peritoneal Chemoperfusion' or HIPEC. Many center perform HIPEC with high dose oxaliplatin, a standard chemotherapy drug active against colon cancer, administered during 30 minutes at 41°C. The hypothesis of this study is, that chemoperfusion at normal (37.5°C) temperature but longer duration (90 minutes) may be safer and at least as efficient. Patients will be treated with one of three possible HIPEC regimens using oxaliplatin: high dose, 30 min, 41°C; high dose, 30 min, 37.5°C; or low dose, 90 min, 37.5°C. The outcome parameters are pharmacokinetic and pharmacodynamic: using specialized techniques, tissue penetration of chemotherapy and cancer cell kill effects will be compared in order to establish the safest and most active HIPEC regimen.

Study Overview

• Status: Completed
• Conditions: Peritoneal Carcinomatosis
• Intervention / Treatment: Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion; Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion; Drug: Hyperthermic intraoperative Peritoneal Chemoperfusion

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium
    • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with peritoneal carcinomatosis from colorectal origin (including appendiceal mucinous neoplasms and the pseudomyxoma syndromes) amenable for cytoreduction and HIPEC.

Exclusion Criteria:

• No written informed consent
• Irresectable and/or metastatic disease found during surgery
• Known allergy to oxaliplatin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxaliplatin 37°C, high dose, 30 minutes	Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion; Dose: 460 mg/m², duration: 30 minutes, temperature 37°C; Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion; Dose: 460 mg/m², duration: 30 minutes, temperature 41°C
Placebo Comparator: Oxaliplatin 41 °C, high dose, 30 minutes	Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion; Dose: 460 mg/m², duration: 30 minutes, temperature 37°C; Procedure: Hyperthermic intraoperative Peritoneal Chemoperfusion; Dose: 460 mg/m², duration: 30 minutes, temperature 41°C
Active Comparator: Oxaliplatin 37°C, low dose, 90 minutes	Drug: Hyperthermic intraoperative Peritoneal Chemoperfusion; Dose: 200 mg/m², duration: 90 minutes, temperature 37°C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity	Scoring of postoperative morbidity according to the Dindo-Clavien system	Until discharge or within 30 days
Mortality	The number of deaths will be recorded.	Until discharge or within 30 days
Area under the perfusate concentration versus time curve (AUC) of platinum	Measurements of platinum in perfusate samples on the high dose interventions.	Before addition of chemotherapy, at 10, 20 and 30 minutes after addition of chemotherapy
Area under the perfusate concentration versus time curve (AUC) of platinum	Measurements of platinum in perfusate samples on the low dose intervention.	Before addition of chemotherapy, at 10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes after addition of chemotherapy
Area under the plasma concentration versus time curve (AUC) of platinum	Measurements of platinum in perfusate samples on the high dose interventions.	Before addition of chemotherapy, at 10, 20, 30,45, 60, 90 minutes and 2, 4, 8, 12, 18, 24 hours after addition of chemotherapy
Area under the plasma concentration versus time curve (AUC) of platinum	Measurements of platinum in plasma samples on the low dose intervention.	Before addition of chemotherapy, at 10, 20, 30, 40, 50, 60, 70, 80, 90 minutes and 2, 4, 8, 12, 18, 24 hours after addition of chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue Concentration (Cmax) of Platinum	Platinum concentration will be measured after removal of perfusate.	after 30 or 90 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: University Ghent
• Investigators: Principal Investigator: Wim P Ceelen, MD, PhD, University Hospital, Ghent

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2012
• Primary Completion (Actual): March 18, 2013
• Study Completion (Actual): March 18, 2013

Study Registration Dates

• First Submitted: April 6, 2012
• First Submitted That Met QC Criteria: April 10, 2012
• First Posted (Estimate): April 11, 2012

Study Record Updates

• Last Update Posted (Estimate): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Peritoneal carcinomatosis from colorectal or appendiceal origin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Digestive System Neoplasms; Abdominal Neoplasms; Carcinoma; Peritoneal Neoplasms
• Other Study ID Numbers: 2012/237; 2012-000701-77 (EudraCT Number)